The Middle Atlantic Region consortium proposes to establish a Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research (RCE) whose theme is "Defense Against Bioterror and Emerging Infection Agents." The proposed Research Projects are: 1) Anthrax (new Bacillus anthracis antigens tested in animal models; compounds to impede anthrax infection; mouse model for imaging germination and bacterial distribution; and development of a mucosal live vector prime/parenteral boost anthrax vaccine); 2) Hemorrhagic Fever and other Emerging Viruses (identification/characterization of neutralizing human monoclonal antibodies reactive to functionally important determinants on Henipaviruses, Bunyaviruses, West Nile, Ebola and Marburg viruses); 3) Poxviruses (subunit variola vaccine; identification of new targets of neutralizing antibody and of vaccinia immune globulin; and development of a mouse ectromelia virus model of smallpox pathogenesis/prevention); 4) Tularemia (conjugate tularemia vaccine; study possible therapy of Francisella tularensis infection using reagents already under clinical testing for sepsis; evaluate currently available bisphosphonate drugs as a first line of defense for individuals exposed to F. tularensis; and attenuated, live-vector tularemia vaccine); 5) Low-Dose Enteric Pathogens (role of type 1 Cryptosporidium parvum candidate genes in pathogenesis/susceptibility to infection as a prelude to vaccine development; Shigella dysenteriae 1 and EHEC vaccines; novel therapeutics for EHEC disease; and diagnostics for detection of these pathogens in water, food, and environmental specimens); and 6) Public Health Response Research (needle-free immunization and vaccine-adjuvanting strategies; immunogenetics of human immune response to smallpox vaccine; and innovative diagnostic platforms for routine clinical use and in known or suspected bioterror events). Three Career Development Projects (to train the next generation of biodefense investigators) and four Developmental Projects (high-risk projects on biodefense agents) will be funded per year. Training will include a Media Training Course; a short course in "GMP Production and Process Development" (in collaboration with Aventis Pasteur Vaccines and Merck Vaccines); a Category A Bioterror Agent Clinical Surveillance Course; a "hands-on" course on working in BSL-3 facilities; and travel awards for RCE scientists and trainees to visit other RCE labs to learn techniques or perform collaborative experiments.